Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

NCT04650581 | Active Not Recruiting Phase 3 Results DMC

• 3 other identifiers: MA402101M041883
• Study Type: interventional
• Target: 250
• Locations: 3 countries
• Sites: 39

Brief Summary

The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Progression-free Survival (PFS) Using RECIST 1.1

  Progression-free survival (PFS) defined as time from randomization to disease progression or death from any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  4 years

Secondary Outcomes (2)

• To Compare the Two Treatment Arms With Respect to Investigator Assessed PFS (Per RECIST 1.1) in the PIK3CA/AKT1/PTEN Altered Cohort

  4 years

• Commencement of Subsequent Line of Systemic Therapy or Death (TSST)

  4 years

Study Arms (2)

Ipatasertib + Fulvestrant

EXPERIMENTAL

Drug: Ipatasertib; Drug: Fulvestrant

Placebo

PLACEBO COMPARATOR

Drug: Fulvestrant; Other: Placebo

Interventions

Fulvestrant DRUG

500 mg IM cycle 1 days 1 and 15 followed by 500 mg IM day 1 q 28 days subsequent cycles

Ipatasertib + Fulvestrant; Placebo

Placebo OTHER

PO QD days 1-21 every 28 days

Placebo

Ipatasertib DRUG

400 mg PO QD days 1-21 every 28 days

Ipatasertib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
• Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
• Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease
• Evidence of clinically and/or radiologically documented disease
• ≥ 18 years of age
• ECOG performance status of 0 or 1
• No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy
• Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting.
• Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study
• Adequate hematology and organ function, in the absence of growth factors
• Absolute neutrophils \> 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin \> 90 g/L
• Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
• ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)

You may not qualify if:

• Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days
• Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption
• Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors
• Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome
• Active or uncontrolled infections or serious illnesses or medical conditions
• Clinically significant liver diseases
• History of lung disease or history of opportunistic infections
• Type 1 or Type 2 diabetes mellitus requiring insulin
• Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia
• Known abnormalities in coagulation
• History of hypersensitivity to the study drugs or components
• Pregnant or lactating women

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Hoffmann-La Roche: collaborator

Study Sites (39)

Southern Highlands Cancer Centre

Bowral, New South Wales, 2576, Australia

Location

Lake Macquarie Private Hospital

Gateshead, New South Wales, 2324, Australia

Location

Gosford Hospital

Gosford, New South Wales, 2250, Australia

Location

Macquarie University Hospital

Macquarie University, New South Wales, 2109, Australia

Location

Shoalhaven Cancer Care Centre

Nowra, New South Wales, 2541, Australia

Location

Sunshine Coast University Hospital

Birtinya, Queensland, 4575, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Victorian Breast and Oncology Care

East Melbourne, Victoria, 3002, Australia

Location

The Northern Hospital

Epping, Victoria, 3076, Australia

Location

Frankston Hospital

Frankston, Victoria, 3199, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

St John of God Bunbury

Bunbury, Western Australia, 6230, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Canberra Hospital

Garran, ACT 2605, Australia

Location

Royal Brisbane and Womens Hospital

Herston, 4029, Australia

Location

BCCA - Cancer Centre for the Southern Interior

Kelowna, British Columbia, V1Y 5L3, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Royal Victoria Regional Health Centre

Barrie, Ontario, L4M 6M2, Canada

Location

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 5W9, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Thunder Bay Regional Health Sciences Centre/

Thunder Bay, Ontario, P7B 6V4, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

Centre Integre de Sante et de Services Sociaux

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

CHA-Hopital Du St-Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Wellington Cancer Centre, Wellington Hospital

Wellington, 2, New Zealand

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ipatasertib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Bingshu Chen, Ph. D.
• Organization: Canadian Cancer Trials Group

bechen@ctg.queensu.ca

613-533-6000

Study Officials

• Stephen Chia

  BCCA - Vancouver Cancer Centre, BC Canada

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: December 2, 2020
• Study Start: January 27, 2021
• Primary Completion: May 23, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 13, 2026
• Results First Posted: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (21); NZ (2); AU (16)